Genes in Predicting Outcome of Patients With DLBCL Treated With Rituximab and Combination Chemotherapy (R-CHOP)

NCT00450385 | Terminated Phase 2 Results DMC

• 3 other identifiers: 20061138SCCC-2006069WIRB-20070073
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 5

Brief Summary

The investigators hypothesize that survival of newly diagnosed DLBCL (diffuse large B-cell lymphoma) patients treated with R-CHOP can be predicted by RNA or protein gene expression or by presence of biomarkers associated with the anti-tumor effects of Rituximab.

Conditions

Lymphoma

Keywords

recurrent adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma; contiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; stage I adult diffuse large cell lymphoma

Outcome Measures

Primary Outcomes (3)

• Determination of a List of Genes and Construction of Survival Prediction Models That Will Predict Overall Survival at 30 Months in DLBCL Patients Receiving R-CHOP Therapy.

  The investigators aim to determine a list of genes and construct survival prediction model(s) that will predict the overall survival at 30 months in DLBCL patients prospectively treated with R-CHOP chemotherapy. Overall survival time will be calculated from the date of the diagnosis until death or last follow-up examination.

  30 months

• Usefulness of Biomarkers Associated With Anti-Tumor Effects of Rituximab in Predicting Overall Survival in DLBCL Patients Receiving R-CHOP Therapy

  The investigators aim to determine the usefulness of biomarkers associated with the antitumor effects of rituximab (e.g. immunoglobulin GFc receptor genotypes, CD20 protein expression and gene expression profiles) to predict overall survival of DLBCL patients treated with R-CHOP therapy and followed for at least 24 months or until death.

  24 Months

• Comparison of the Ability of Constructed Survival Models to Predict Overall Survival in DLBCL Patients Receiving R-CHOP Therapy

  The investigators will compare the ability of constructed survival models to predict survival in DLBCL patients receiving R-CHOP therapy

  2 Years

Secondary Outcomes (3)

• Determination of the Ability of Models and/or Biomarkers Associated With Anti-Tumor Effects of Rituximab to Predict 24-month Time to Treatment Failure in DLBCL Patients Receiving R-CHOP Therapy

  24 Months

• Overall Response Rate of Study Participants at the End of Protocol Therapy

  Up to 8 cycles, about 24 weeks

• Number of Participants From Whom Fixed Tissue Samples Were Collected for Future Studies.

  Baseline

Study Arms (1)

R-CHOP

EXPERIMENTAL

Patients will receive R-CHOP for 6 to 8 cycles: * Rituximab 375 mg/m2 on day 1 * Cyclophosphamide 750 mg/m2 IV on day 1 * Doxorubicin 50 mg/m2 on day 1 * Vincristine 1.4 mg/m2 (maximum = 2 mg) IV on day 1 * Prednisone 100 mg orally days 1-5, repeated every 21 days.

Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Vincristine

Interventions

Rituximab DRUG

Rituximab 375 mg/m2 on day 1 for 6 to 8 cycles

Also known as: Rituxan

R-CHOP

Cyclophosphamide DRUG

Cyclophosphamide 750 mg/m2 IV on day 1 for 6 to 8 cycles

Also known as: Cytoxan

R-CHOP

Doxorubicin DRUG

Doxorubicin 50 mg/m2 on day 1 for 6 to 8 cycles

Also known as: Adriamycin

R-CHOP

Prednisone DRUG

Prednisone 40 mg/m2 orally days 1-5, repeated every 21 days for 6 to 8 cycles.

Also known as: Deltasone

R-CHOP

Vincristine DRUG

Vincristine 1.4 mg/m2 (maximum = 2 mg) IV on day 1 for 6 to 8 cycles

Also known as: Oncovin

R-CHOP

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Diagnosis of diffuse large B-cell lymphoma, CD20-positive, according to the World Health Organization Classification, stages II-IV or limited stage I disease that is bulky (more than 10 cm) or with International Prognostic Index (IPI) score \> 1.
• \. Patients must not have had prior chemotherapy, radiotherapy or immunotherapy. A short course (\< 2 weeks) of corticosteroids is allowed.
• \. Adequate paraffin-embedded tumor specimen must be available for gene expression analysis and immunohistochemistry prior to initiation of therapy. (If the specimen is deemed inadequate, the subject can be retroactively screen failed, as this does not change the treatment regimen).
• \. Baseline measurements and evaluation must be obtained within 4 weeks before first treatment.
• \. Age \>18 years.
• \. Eastern Cooperative Oncology Group (ECOG) performance status 0-3.
• \. Adequate organ function:
• White Blood Cells count (WBC) \>2500/µL
• Absolute Neutrophil Count (ANC) \> 1000/µL (unless due to disease in marrow)
• platelet count \>100,000/µL (unless due to disease in marrow)
• creatinine \< 2.0 mg/dL,
• bilirubin \< 1.5 mg/dL (may be 1.5-3.0 mg/dl if due to liver involvement by lymphoma)
• Serum Glutamic Oxaloacetic Transaminase (SGOT)/ Serum Glutamic Pyruvic Transaminase (SGPT) \<3 x upper limit of normal.
• \. Female patients must not be pregnant or breast feeding.
• \. Women of childbearing potential and men must be strongly advised to use an accepted and effective method of contraception.

You may not qualify if:

• \. Patients with a second malignancy other than basal cell carcinoma of the skin or in situ carcinoma of the cervix unless the tumor was treated with curative intent at least two years previously; and; the patient continue to be free of evidence of recurrence.
• \. Patients with HIV infection as these patients are managed on dedicated protocols.
• \. Patients with active central nervous system (CNS) lymphoma.

Sponsors & Collaborators

• University of Miami: lead

Study Sites (5)

Stanford University

Stanford, California, 94305, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University of Rochester Medical Center - Wilmot Cancer Institute

Rochester, New York, 14642, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Lymphoma; Lymphoma, Large B-Cell, Diffuse

Interventions

Rituximab; Cyclophosphamide; Doxorubicin; Prednisone; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Results Point of Contact

• Title: Izidore Lossos MD
• Organization: University of Miami

ilossos@med.miami.edu

305-243-4785

Study Officials

• Izidore S. Lossos, MD

  University of Miami

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 20, 2007
• First Posted: March 22, 2007
• Study Start: April 24, 2007
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: June 23, 2017
• Results First Posted: June 23, 2017

Record last verified: 2017-05

Locations

US (5)